JPH0660133B2 - New homopropargyl amines - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to novel homopropargylamines, a process for producing the same, and use as an antifungal agent.

[Structure of Invention]

This invention has the formula (I) [In the Formula, n is 2 or 3, R ₁ is Formula (IIa), (IIb) or (IIc) (Wherein R ₆ and R ₇ are independently H, halogen,
CF ₃ , lower alkyl or lower alkoxy, s is 3-
A number of 5, X represents O, S or OCH ₂ ) R ₂ is H or lower alkyl, R ₃ and R ₄ are independently H or lower alkyl, or R ₃ and R ₄ Together (CH ₂ )
_u (where u represents a number of 3-5) and R ₅ is H, alkenyl, or alkyl, trialkylsilyl, dialkylphenylsilyl, phenyl, phenylalkyl and cycloalkyl ( here,
Alkyl, phenyl and cycloalkyl groups or moieties are unsubstituted or substituted with OH, lower alkyl, lower alkoxy, phenyl or halogen)
And a free base form of the novel homopropargylamines or an acid addition salt thereof.

This invention also provides (a) formula (III) [Wherein R ₁ , R ₂ , R ₃ and R ₄ have the above-mentioned meanings], a compound represented by the formula (IV) A- (CH ₂ ) _n- C≡CR ₅ (IV) ₅ and n are as defined above, A is a leaving group which can be separated under the reaction conditions], or (b) Formula (V) [Wherein R ₁ , R ₂ , R ₃ , R ₄ and n are as defined above] in a metal form with a corresponding dialkylphenylsilylhalogen, trialkylsilylhalogen or oxoalkane compound Let formula (Ia) [Wherein R ₁ , R ₂ , R ₃ , R ₄ and n are as defined above, ▲ R ^I ₅ ▼ is dialkylphenylsilyl, trialkylsilyl or α-hydroxyalkyl] Or (c) formula (Ia) (wherein R ^I ₅ ▼ is α-hydroxyalkyl) is dehydrated to give the corresponding formula (I) (wherein R ₅ is 1
-Alkene-1-yl), wherein the desired functional groups can be protected during the reaction with protecting groups,
In this case, there is provided a process for producing a compound of formula (I), which comprises removing the protecting group after completion of the reaction.

The compounds of formula (I) are obtained in free base form or in acid addition salt form. The free base form of the compounds of formula (I) can be converted into the acid addition salt form, and vice versa, by conventional methods.

Process (a) is, for example, a solvent inert under the reaction conditions, for example a lower alcohol such as ethanol optionally mixed with water, an aromatic hydrocarbon such as benzene or toluene, a cyclic ether such as dioxane, or It can be carried out in a carboxylic acid-N, N-dialkylamide such as dimethylformamide. The reaction temperature is preferably room temperature or the boiling point of the reaction mixture. This reaction is also
Preference is given to carrying out in the presence of an acid binder, for example an alkali metal carbonate such as Na ₂ CO ₃ .

Process (b) can be carried out, for example, in a solvent inert under the reaction conditions, for example, a cyclic ether such as tetrahydrofuran, under dehumidifying conditions, preferably at a low temperature.

The dehydration of the method (c) is a method known per se, for example, p-
In the presence of a base such as triethylamine, using toluenesulfonic acid or by treatment with mesyl chloride,
It can be carried out in a solvent which is inert under the reaction conditions, for example CH ₂ Cl ₂ .

The compounds of formula (I) can contain one or more chiral centers and / or double bonds. These are generally obtained in the form of racemates, diastereomers and / or cis / trans mixtures. However, such mixtures may, if desired, be fully or partially resolved using known methods to give the individual compounds or the desired mixture.

The alkyl group may be straight or branched and has a carbon atom of 1-1.
It can contain 2, preferably 1-8, especially 1-5.

The lower alkyl and lower alkoxy substituents preferably have 1-4, more preferably 1-2 carbon atoms.

Suitable halogen substituents of compounds of formula (I) are, for example, F, C
l and Br.

When R ₅ is alkenyl, preferably 3-6, especially 3
Or it contains 4 carbon atoms and represents, for example, allyl or propenyl.

When R ₅ is cycloalkyl, it is preferably 3-carbon atoms.
Including 6 pieces.

When R ₅ is phenylalkyl, phenylC _1-5 alkyl is preferred.

When R ₅ is alkyl, alkenyl or phenylalkyl, it is preferably branched at the alpha position of the acetylene bond. Particularly preferred alkyl and phenylalkyl for R ₅ are tertiary alkyl and phenyl-substituted forms thereof, in which case these groups may be unsubstituted or substituted as described above.

In the compound of formula (IV), A is for example halogen, especially Cl
Or Br, or an organic sulfonyloxy group having 1 to 10 carbon atoms, such as alkylsulfonyloxy (especially having 1 to 4 carbon atoms), for example, methylsulfonyloxy, or alkylphenylsulfonyloxy (especially 7-carbon atoms). 10), for example tosyloxy.

The starting materials are known or are prepared in a manner known per se or by methods analogous to those described herein.

The compounds of formula (I) have chemotherapeutic activity. In particular, according to an in vitro test, Trychophyton spp., Aspergillus spp., Microsporum spp., Sporotrix schenkii, Candida sp.
It shows antifungal activity against various families and types of fungi including ida spp.) at a concentration of, for example, 0.003 to 50 μg / ml. Shows activity. In the latter case, the test substances are administered 24 hours after infection, daily for 7 days, topically by rubbing the test substance (dissolved in polyethylene glycol) onto the skin surface or by oral administration. Candida activity, especially in compounds where R ₁ is IIb, is shown in the vagina commonly used in mice or rats,
Revealed in intrauterine or disseminated infection models. For example, it is active when administered locally at a concentration of 0.01 to 0.2%. Orally administered activity is demonstrated in in vivo studies of guinea pig trichophytonosis, for example at doses of 2 to 70 mg / kg.

Therefore, the compounds of this invention are useful as antifungal agents.

The compounds of this invention can be used in either the free base form or the chemotherapeutic acceptable salt form. Such salts exhibit the same order of activity as the free base. Suitable salts are, for example, the hydrochloride, acidic fumarate or naphthalene-1,5-disulfonate. The compounds of this invention are
Compounds with similar chemotherapeutic uses such as griseofulvin can be used in analogy to known methods and can be administered parenterally, topically, intravenously or orally.

Accordingly, the present invention provides a method for treating subjects in need of treatment.
A method for treating a disease or infection caused by a fungus, which comprises administering an effective amount of a free base of a compound of (I) or a chemotherapeutically acceptable acid addition salt, and a chemotherapeutic agent, particularly an antifungal agent. Also relates to the use of the free base of the compound of formula (I) or a chemotherapeutic acceptable acid addition salt thereof.

The compounds of this invention can be mixed with conventional chemotherapeutic acceptable diluents or carriers, and optionally other adjuvants, and administered in the form of tablets or capsules, eg orally. The compounds of this invention may also be administered topically (in conventional dosage forms such as ointments or creams), parenterally or intravenously. The amount and concentration of active substance will, of course, vary depending on the compound used, the intended treatment and the nature of the dosage form. However, in general, for example in topical dosage forms, 0.05-5% by weight, especially 0.1-1% by weight concentrations give satisfactory results.

For oral administration, a suitable total daily dose is about 70-2000 mg.
This is a dose of about 17.5-1000 mg 2-4 times a day.
The dosage form or sustained release preparation is suitable for multiple administration.

The free base form or the agriculturally acceptable acid addition salt form of the compound of formula (I) (hereinafter referred to as pesticide of the present invention) is useful for controlling phytopathogenic fungi. Interesting antibacterial activities include rust diseases such as Uromyces appendiculatus in pods (runner beans) and Puccinia in wheat, and Erysiphe cichoracearum in cucumber, E. Graminis in wheat, Podosphaera leveotricha in apples,
Uncinula necat in grapes
or) powdery mildews are observed in in vivo experiments carried out at test concentrations of 0.5-500 ppm. The test results also show that the plants are well tolerated.

Therefore, the pesticides of the present invention include plant pathogenic fungi such as Puccinia spp., Hemileia spp., Uromyces sp.
Basidinmycet of Uredinales (Uromyces spp.)-Like Uredinales
es), Erysiphe spp.,
It is used for controlling or killing Ascomycetes of Erysiphales such as Podosphaera spp. And Uncinula spp.

The use amount of the pesticide of the present invention is, compound to be used, treatment target (plant, soil, seed), treatment method (eg, spraying, sprinkling, coating), treatment purpose (prevention or treatment), type of fungus to be treated, And various factors such as application time.

Generally, for plant or soil treatment, the pesticides of the invention are used in amounts of about 0.005 to 2.0, preferably about 0.01 to 1 kg / ha, with satisfactory results. For example, in a crop such as shellfish, per hectare,
0.04 to 0.125 kg of active ingredient or 1 active ingredient per hl in agricultural crops such as fruits, vineyards and vegetables
~ 5 g concentration. (The amount applied depends on the size of the crop or the amount of leaves, but is from 300 to 1000 / ha, which equates to an application rate of about 10 to 50 g / ha.) If desired, the treatment may be for example 8 to 30 days. Can be repeated at intervals of.

When the pesticide of the present invention is used for seed treatment, it is about 0.05 to
Satisfactory results are generally obtained with the compounds according to the invention in an amount of 0.5, preferably about 0.1 but not 0.3 g / kg seed.

The agriculturally acceptable salt forms of the pesticides of this invention generally have the same order of activity as the free base form of the corresponding compound.

As used herein, the term soil shall include any conventional cultivation medium, natural or artificial.

The compounds of the present invention include soybeans, coffee, ornamental plants (particularly geranium, roses), vegetables (eg, legumes, cucumbers, celery, tomatoes and bean plants), sugar beets, sugar cane, peanuts, cotton, flax, Corn (corn), vineyards, fruits (apples, corns, prunes, bananas) and shells (eg, wheat, mustard, barley,
It can be used for many agricultural crops such as rice.

Accordingly, the present invention provides a phytopathogenic fungus, which comprises applying an antifungal effective amount of the compound of formula (I) in free form or in an agriculturally acceptable acid addition salt form to the fungus or its potential sites. The present invention provides a method of suppressing the above.

The present invention also comprises a free form of the compound of formula (I) or an agriculturally acceptable acid addition salt form thereof as an antifungal agent and an agriculturally acceptable diluent (hereinafter referred to as a diluent), if desired. An antifungal composition is provided that includes other additives such as surfactants. The composition generally contains 0.0005-90% by weight of active ingredient, for example 0.001-70% by weight.

The term diluent as used herein refers to a liquid or solid agriculturally acceptable material capable of diluting the active ingredient in addition to the active ingredient in an easy and good application form, i.e. to a usable or desired strength of activity. Means Examples of such diluents are talc, kaolin, diatomaceous earth, xylene or water.

The above-mentioned preparations, in particular those used in the form of sprays such as concentrates for water dispersion or wettable powders, are, for example, condensation products of formaldehyde and naphthalene sulfonate, alkylaryl sulfonates, lignin sulfonates, aliphatic alkyl sulfonates, ethoxylated alkylphenols and ethoxys. Surfactants such as wetting and dispersing agents such as epoxidized fatty alcohols (eg up to 20% by weight) can be included.

In addition to the usual diluents and surfactants, the compositions according to the invention also have additives for special purposes such as stabilizers, deactivators (in the case of solid formulations with carriers having an active surface), plants. Adhesion improvers, corrosion inhibitors, antifoams and dyes can be included. Further, for example, sulfur,
Chlorothalonil and Mancozeb (manconeb), Maneb (maneb), Zineb (zineb), Probineb (propineb)
Dithiocarbamates such as, and captans (capt
an), captafol and horpets (fo)
Other useful substances such as trichloromethane-sulfenylphthalimide and analogs such as lpet), benzimidazoles such as benomyl and carbendazim or pesticides may be present in the formulation .

Examples of antifungal agents for plants are as follows.

a. Powder formulation for hydration 10 parts of compound of formula (I) 4 parts synthetic fine silica 4 parts sodium lauryl sulphate 7 sodium lignin sulphonate
Parts, 66 parts of finely powdered kaolin and 10 parts of diatomaceous earth are mixed and ground to give a powder having an average particle size of about 5 microns. The resulting wettable powder is diluted with water before being used as a spray. It is used for foliar spray and root dip applications.

b. Granules 0.5 parts by weight of a binder (nonionic surfactant) is sprayed on 94.5 parts of quartz sand put in a tumbler mixer, and the whole is thoroughly mixed. Then, 5 parts by weight of the compound of formula (I) is added and mixed well to obtain a granule preparation having a particle size range of 0.3 and a particle size of 0.7 mm.

c. Thick emulsion 25 parts by weight of the compound of formula (I) are mixed with 10 parts by weight of emulsifier and 65 parts by weight of xylene. This concentrate is diluted with water to the desired concentration.

d. Seed Dressing 45 parts of the compound of this invention are mixed with 1.5 parts of diamylphenol decaglycol ether / ethylene oxide adduct, 2 parts of spindle oil, 51 parts of finely divided talcum and 0.5 part of Rhodanine B dye. The mixture is ground with a contraplex mill at 10,000 rpm to an average particle size of 20 microns or less. The resulting dry powder has good stickiness and can be applied to seeds, for example by mixing for 2 to 5 minutes in a loosely rotating container.

Among the compounds of formula (I), preferred compounds are those in which the substituents have one or more of the definitions given below.

R ₁ is a group of formula (IIa) or (IIb), X is O or S, R ₆ is hydrogen, R ₇ is H, halogen (especially Cl or Br) or C _1-4 alkyl ( In particular CH ₃ ), R ₂ is H or C _1-4 alkyl, R ₃ is H, or together with R ₄ is — (CH ₂ ) ₄ —, R ₄ is C _1-4 Alkyl and R ₅ is H, C _1-8 alkyl (especially C _1-5 alkyl), C _3-6 cycloalkyl, C _3-5 alkenyl, C _1-4 alkoxy-C _1-5
Alkyl, phenyl-C _1-5 alkyl, halogenophenyl-C _1-5 alkyl, hydroxy-C _1-5 alkyl, tri (C
_1-5 alkyl) silyl and di (C _1-5 alkyl) phenylsilyl.

Among the compounds of formula (I), particularly preferred compounds are those in which the substituents have one or more of the definitions defined below. R ₁ is a 1-naphthyl, benzofuranyl or benzo [b] thienyl group (wherein said group is unsubstituted or monosubstituted with halogen (especially Cl or Br) or C _1-4 alkyl (especially CH ₃ ). R ₂ and R ₃ are H, R ₄ is CH ₃ or C ₂ H ₅ , especially CH ₃ , and R ₅ is H, C _3-6
Cycloalkyl or C _4-5 alkyl, C _1-4 alkoxy-C _3-5 alkyl, halogenophenyl-C _3-5 alkyl, phenyl-C _3-5 alkyl or hydroxy C _3-5
It is a tertiary group selected from alkyl (the group being linked to the homopropargyl group by a tertiary carbon atom).

〔Example〕

The present invention will be described below with reference to examples. Temperatures are given in degrees Celsius.

Example 1 Preparation of N-methyl-N- (1-naphthylmethyl) -5,5-dimethyl-3-hexyne-amine.

To a solution of 540 mg of 5,5-dimethyl-3-hexyn-1-ol in dimethylformamide (DMF) is added at 0 ° C. 1.2 ml of triethylamine. Then, under stirring,
0.335 ml of methanesulfonyl chloride is added dropwise. After stirring for 2 hours at room temperature, 740 mg of N-methyl-1-naphthylmethylamine are added and the mixture is heated at 80 ° C. overnight. The solvent is evaporated under reduced pressure, the residue is partitioned between saturated aqueous NaHCO ₃ solution and ethyl acetate, and the organic layer is washed, dried and concentrated. The crude residue was subjected to silica gel chromatography (toluene / ethyl acetate = 9/1 used) to give the title compound (Compound 1)
As an oil.

Example 2 In the same manner as in Example 1, the following compound contained in the formula (I) is obtained.

Example 3 Preparation of N-methyl-N- (1-naphthylmethyl) -5-ethyl-5-hydroxy-3-heptin-amine.

To an anhydrous tetrahydrofuran (THF) solution of 2 g of N-methyl-N- (1-naphthylmethyl) -3-butyne-amine, at -70 ° C, 5.6 ml of a 15 wt% hexane solution of N-butyllithium was added dropwise. After hours, at -70 ° C, 0.95 ml of diethyl ketone is added dropwise. The mixture is stirred at room temperature for 3 hours, poured onto ice and extracted with ether. The organic layer is washed, dried and concentrated under reduced pressure. Title compound (Compound 2
5) is obtained as an oil by silica gel chromatography (toluene / ethyl acetate = 3/1 used).

Compounds 26, 27 and 28 are obtained as described in Example 3.

Example 4 Preparation of N-methyl-N- (1-naphthylmethyl) -5-ethyl-5-hepten-3-yn-amine.

N-Methyl-N- (1-naphthylmethyl) -5-ethyl-5-hydroxy-heptin-amine 630 mg CH ₂ Cl ₂
To the solution at −20 ° C. is added dropwise 0.5 ml of triethylamine and then 0.21 ml of mesyl chloride dissolved in CH ₂ Cl ₂ . The mixture is stirred at room temperature for 3 hours, washed several times with water, the organic layer is dried and concentrated. The residue is subjected to silica gel chromatography (toluene / ethyl acetate = 4/1 used) to give the title compound (Compound 29) as an oil.

Intermediate (A) 5,5-Dimethyl-3-hexyn-1-ol.

In an anhydrous THF solution of 3.1 g of 3,3-dimethyl-1-butyne,
At −20 ° C., 28.3 ml of 1.6M hexane solution of n-butyllithium is added dropwise. After 1 hour at -50 ° C, hexamethylphosphoric triamide was added to give 1.
Add 40 ml of 4M ethereal solution. The mixture is stirred overnight and then mixed with water. The aqueous layer is extracted with ether, and the organic layer is dried and concentrated (normal pressure). The residue is distilled under reduced pressure with a water pump to give the title compound as an oil, bp 70 ° C / 16 torr.

The following intermediates belonging to formula (IV) can be obtained in the same manner as in the above method (A).

(I) 3- (4-fluorophenyl) -3-methyl-1-
Butin.

a) 3- (4-Fluorophenyl) -3-methyl-2-butanone.

A solution of 5.84 g of 2- (4-fluorophenyl) -2-methylpropionitrile in anhydrous diethyl ether was added at -30 ° C.
In, 22 ml of 1.6M diethyl ether solution of methyllithium is added dropwise under inert gas. Then the cooling bath is removed and the mixture is stirred at room temperature for 3 hours. The reaction mixture is poured into ice, the organic layer is stirred with 6N-HCl overnight, the acid is separated off, washed with water, dried and concentrated under reduced pressure. The obtained oily residue is used for the next reaction without purification.

NMR: 6.8-7.4 (m, 4H), 1.94 (s, 3H), 1.5 (s, 6H) b) 3- (4-Fluorophenyl) -3-methyl-1-butyne.

4.8 g of 3- (4-fluorophenyl) -3-methyl-2-butanone are stirred with 11 g of phosphorus pentachloride and 60 ml of CCl ₄ at room temperature for 1 hour. The mixture is poured onto ice, the organic layer is separated, washed, dried and concentrated under reduced pressure. The residue is dissolved in dimethylsulfoxide (DMSO), added dropwise to a mixture of 3 g of powdered KOH and 50 ml of DMSO and heated at 120 ° C. overnight. The mixture is poured onto ice, extracted with pentane, the organic layer is washed, dried and concentrated to give the title compound, bp 72-75 ° C / 14 torr.

(K) N-methyl- (2H-1-benzopyran-4-yl) methanamine.

3 g of 4-chloromethyl-2H-1-benzopyran is added dropwise to 30 ml of a 33% solution of methanamine in ethanol.
The mixture was stirred at room temperature overnight, concentrated under reduced pressure, and the residue was diluted with 1N-
Dissolve in HCl and extract with CH ₂ Cl ₂ . The acidic layer is made alkaline, extracted with CH ₂ Cl ₂ , and the organic layer is washed, dried and concentrated to give the title compound.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI Technical display location A61K 31/34 7431-4C 31/35 7431-4C 31/38 7431-4C 31/40 7431-4C 31/445 7431-4C 31/55 7431-4C 31/695 8314-4C C07C 215/08 7457-4H 217/08 7457-4H C07D 207/08 8217-4C 211/14 9165-4C 211/20 9165-4C 211/22 9165-4C 223/04 227/04 307/79 307/82 307/83 311/58 9360-4C 333/54 333/62 333/64 405/04 207 7602-4C 211 7602-4C 223 7602- 4C 409/04 207 7602-4C 211 7602-4C 223 7602-4C C07F 7/10 A 8018-4H

Claims (5)

[Claims] 1. A formula (I) [In the formula, n is 2 or 3, and R ₁ is the formula (IIa), (IIb) or (IIc) (Wherein R ₆ and R ₇ are independently H, halogen, CF ₃ , lower alkyl or lower alkoxy, s is a number of 3-5, X
Represents O, S or OCH ₂ ) R ₂ is H or lower alkyl, R ₃ and R ₄ are independently H or lower alkyl,
Or R ₃ and R ₄ together are (CH ₂ ) _u (where u represents a number of 3-5), R ₅ is H, alkenyl, or alkyl, trialkylsilyl, Dialkylphenylsilyl, phenyl,
Means groups selected from phenylalkyl and cycloalkyl, where the alkyl, phenyl and cycloalkyl groups or moieties are unsubstituted or substituted with OH, lower alkyl, lower alkoxy, phenyl or halogen, respectively. The free base form or acid addition salt of the homopropargyl amines represented by 2. R ₁ is a group of formula (IIa) or (IIb), X is O or S, R ₆ is hydrogen, R ₇ is H, halogen or C _1-4 alkyl. , R ₂ is H or C _1-4 alkyl, R ₃ is H, R ₄ is C _1-4 alkyl, or R ₃ and R ₄ together are — (CH ₂ ) ₄ — R ₅ is H, C _1-8 alkyl, C _3-6 cycloalkyl, C _3-5 alkenyl, C _1-4 alkoxy-C _1-5 alkyl, phenyl-C
_1-5 alkyl, halogenophenyl-C _1-5 alkyl, hydroxy-C _1-5 alkyl, tri (C _1-5 alkyl) silyl,
The compound of claim 1 which is di (C _1-5 alkyl) phenylsilyl. 3. R ₁ is a 1-naphthyl, benzofuranyl or benzothiophenyl group (wherein these groups are unsubstituted,
Or halogen or C _1-4 alkyl mono-substituted), R ₂ and R ₃ are H, R ₄ is C _1-4 alkyl, R ₅ is H, C _3-6 cycloalkyl Or C _3-5 alkyl, C _1-4 alkoxy-C _3-5 alkyl, halogenophenyl-C _3-5 alkyl, phenyl-C _3-5 alkyl or hydroxy C _3-5 alkyl (the above groups are Bonded to a homopropargyl group by a tertiary carbon atom) third selected from
The compound according to claim 2, which is a secondary group. 4. Formula (I) [In the formula, n is 2 or 3, and R ₁ is the formula (IIa), (IIb) or (IIc) (Wherein R ₆ and R ₇ are independently H, halogen, CF ₃ , lower alkyl or lower alkoxy, s is a number of 3-5, X
Represents O, S or OCH ₂ ) R ₂ is H or lower alkyl, R ₃ and R ₄ are independently H or lower alkyl,
Or R ₃ and R ₄ together are (CH ₂ ) _u (where u represents a number of 3-5), R ₅ is H, alkenyl, or alkyl, trialkylsilyl, Dialkylphenylsilyl, phenyl,
Means groups selected from phenylalkyl and cycloalkyl, where the alkyl, phenyl and cycloalkyl groups or moieties are unsubstituted or substituted with OH, lower alkyl, lower alkoxy, phenyl or halogen, respectively. A medicinal antifungal agent comprising a free base form or an acid addition salt form of homopropargylamines represented by 5. Formula (I) [In the formula, n is 2 or 3, and R ₁ is the formula (IIa), (IIb) or (IIc) (Wherein R ₆ and R ₇ are independently H, halogen, CF ₃ , lower alkyl or lower alkoxy, s is a number of 3-5, X
Represents O, S or OCH ₂ ) R ₂ is H or lower alkyl, R ₃ and R ₄ are independently H or lower alkyl,
Or R ₃ and R ₄ together are (CH ₂ ) _u (where u represents a number of 3-5), R ₅ is H, alkenyl, or alkyl, trialkylsilyl, Dialkylphenylsilyl, phenyl,
Means groups selected from phenylalkyl and cycloalkyl, where the alkyl, phenyl and cycloalkyl groups or moieties are unsubstituted or substituted with OH, lower alkyl, lower alkoxy, phenyl or halogen, respectively. An antifungal agent for agriculture, which comprises the free base form or acid addition salt form of homopropargylamines represented by